Cancer Research in C. elegans
C. elegans C. elegans are free living nematodes that grow to about 1mm long and are transparent, which is useful in genetic studies. These nematodes lack a respiratory and circulatory system. They are unsegmented and bilaterally symmetrical. They were also the first multicellular organism to have its entire genome sequenced. This is one of the reasons that they have been described as a model organism. They also have a very simple nervous system and they are easy to grow in bulk populations. It is also a good study organism because it has an essentially invariant somatic cell lineage. The transparency lends itself to cellular study and some other developmental processes. Research Cancer is caused by mutations in many genes, leading to a complex phenotype.'' In previous research, there have been gain-of-function mutations identified in receptor tyrosine kinases. One main example is c-Met in lung cancer. Lung cancer is particularly deadly, wtih only 15% of patients surviving more than 5 years after diagnosis. This particular research group previously used mice to study the mutations in c-Met, but the experiments take a long time and are expensive and the numbers of animals are limited. ''C. elegans provides a cheaper, more rapid alternative. EGFR (epidermal growth factor receptor), which is highly altered in lung cancer by mutations and amplifications, has been shown to cause altered vulval phenotypes. c-Met is similar to EGFR, which is a known oncogene. c-Met over-expression and amplification has been shown in many forms of human cancer. The researchers used both human wild type nematodes and c-Met mutant nematodes for the study. The vulval development of each nematode was observed visually. The fecundity and viability of each nematode was tested, along with immunoblotting and performing PCR to verify that c-Met was being expressed. In nematodes with c-Met overexpression, there were many abnormal phenotypes, from growth stoppage to abnormal locomotion to abnormal vulva formation. These results were as predicted from other studies on cell and animal models. The biggest affect that c-Met had on the nematodes was in terms of viability, from 70% in the wildtype to an average of 25% in the mutants. To test whether the c-Met mutation is most common in smokers, the researchers exposed the nematodes to nicotine. When exposed for 24 hours or more, there was a significant increase in the degree of vulval developmental defects and many of the other phenotypic defects. In addition to the abnormal locomotion observed in the first trials, the addition of nicotine lead to an increase in complete paralysis. Conclusions The conclusions are that the c-Met mutation results in higher probability of developmental defects and reduced viability, which is increased when exposed to nicotine. The results showed that the mutant cells are able to escape the negative regulation that is normally present, and perpetuate the lung cancer cells. They also determined that there could be a genetic component to lung cancer, and smoking increases the risk, as not every smoker gets lung cancer. The c-Met mutations and altered phenotypes that were shown in this study can be reflected in patients with lung cancer. The main result of the study was that it was determined that C. elegans is a good organism for studying cancer in the context of a whole organism. Resources Eyewire: The Story of C. Elegans Cancer Biology and Therapy: C. elegans as a model organism for in vivo screening in cancer Wikipedia: C. elegans